Retroviral vectors are capable of transferring genes with high efficiency and stability to host cells. Thus, they are used in gene transfer methods, for transferring genes into cells in a variety of fields including the field of medicine. Generation of retroviral vectors has been developed based on the genetic structure and the life cycle mechanism of retroviruses. The fundamental principle is to transfer the gene of interest into a retroviral vector possessing a packaging signal but lacking each of the gag, pol, and env structural genes, then introducing the retroviral vector into a packaging cell possessing each of the gag, pol, and env structural genes lacking a packaging signal. Then, a virus particle containing the retroviral vector RNA is formed (i.e. packaged), and finally, retroviruses are produced into the supernatant of a cell culture (Kitamura, T., International Journal of Hematology, 67:351–359 (1998)). Retroviruses produced in this manner can efficiently transfer the genes of interest into cells. Simultaneously, since they lack each of the gag, pol, and env structural genes, they can replicate only within the packaging cells and cannot replicate within normal cells. Therefore, functional retroviruses are unlikely to regenerate from the prepared infected cells.
The production of packaging cells with such characteristics is disclosed in international publication numbers WO90/02806, WO94/19478, WO96/34098, and so on. However, the prior art is unsatisfying in terms of infection efficiency and long-term stability. In addition, to increase the titer of the viruses, it is necessary to express the viral structural proteins in a large amount within the packaging cell. Packaging cells that can express a large amount of viral structural proteins and show a limited reduction in titer of viruses produced through passages are needed in the art.